Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
  • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
  • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
  • C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

• the end products of the process of the subject invention are 1-loweralkyl-pyrrole-2-acetates (I) which have been reported in the literature as being useful intermediates in the preparation of 5-aroyl-pyrrole-2-acetic acid derivatives having anti-inflammatory activity (e.g., see U.S. Patent Nos. 3 752 826, 3 803 169, 3 846 447 and 3 957 818).
• This invention relates to an improved process of preparing loweralkyl 1-loweralkyl-pyrrole-2-acetates of the general formula(I) wherein R is loweralkyl, preferably methyl; and alk is loweralkyl, preferably methyl.
• an improved process of reducing a loweralkyl 1-loweralkyl- pyrrole-2-glyoxylate to a loweralkyl 1-loweralkyl-pyrrole-2-acetate by the amine-catalyzed action of hydrogen sulfide in a tertiary amine solvent or a dipolar aprotic organic solvent the improvement comprising the reduction being conducted under a pressure of at least 2.11 kg/cm 2 . Accordingly, a marked increase in percent conversion from glyoxylate precursor to acetate product is obtained.
• loweralkyl refers to straight or branch chained alkyls having from 1 to 6 carbons, for example, methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, pentyl, hexyl and the like.
• the most preferred amines are pyridine, imidazole and N-methylpiperidine.
• Base catalysts which are liquids and also suitable as solvents for the reduction reaction, e.g., pyridine, triethylamine and the like, may be employed without the use of additional solvent.
• solvents that may be utilized for the redue '.on reaction, although less preferred,are dipolar aprotic organic solvents, such as, for example, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylphosphoramide (HMPA) and the like.
• DMF N,N-dimethylformamide
• DMSO dimethyl sulfoxide
• HMPA hexamethylphosphoramide
• reaction temperature is not critical and temperatures varying from ambient temperature to about 120°C may be conveniently utilized, although elevated temperatures are advantageously employed to enhance the rate of reaction and temperatures varying from about 60°C to about 100°C are preferred.
• the reduction reaction is run in an appropriate sealed vessel capable of withstanding an internal pressure of at least 2.11 kg/cm 2 of gaseous hydrogen sulfide.
• the preferred pressure range is from about 3.52 to about 35.2 kg/cm 2 although pressures up to about 70.3 kg/cm 2 may be employed.
• a solution of 50g of methyl 1-methylpyrrole-2- glyoxylate in 200 ml of pyridine is cooled to -78°C and 64g of hydrogen sulfide is added.
• the mixture is sealed in a stirred autoclave and heated to 63°C.
• the pressure srises to about '9.14 kg/cm 2 .
• the hydrogen sulfide is driven off in a nitrogen stream and the solution is decanted from the precipitated sulfur.
• Pyridine is distilled off at 20 mm Hg.
• the residue is distilled at 0.03 mm Hg, b.p. 68-70°C, to give 39.2g of oily methyl l-methylpyrrole-2-acetate (86% yield).
• a solution of 25g of methyl l-methylpyrrole-2- glyoxylate, 23g of hydrogen sulfide and 100 ml pyridine is sealed in an autoclave and stirred 46 hrs. at 25°C under pressure of 4.22 kg/cm 2 . The pressure is released and the solution decanted from precipitated sulfur.
• the solution is taken up in diethyl ether and washed successively with potassium carbonate solution, dilute hydrochloric acid, sodium bicarbonate solution and brine. The solution is then dried over MgS0 4 and the solvent evaporated in vacuo.
• the residual oil is distilled at 0.001 to 0.005 mmHg to give 18.8 g of oily methyl 1-methylpyrrole-2-acetate (82% yield).
• a solution of 44 g (0.26 mole) of methyl N-methyl-2-pyrrole-2-glyoxylate in 110 g (1.4 mole) of pyridine is placed in a stirred autoclave.
• the solution is pressurized with hydrogen sulfide gas, with stirring, until the pressure is stabilized at about 14.1 kg/cm 2 . Stirring is continued at room temperature for four hours.
• the pressurized vessel is opened and the contents assayed by gas liquid chromatography (GLC) indicating 33 % of the product, methyl 1-methyl- pyrrole-2-acetate.
• a mixture of 1 g of the loweralkyl 1-methylpyrrole-2-glyoxylate and quantities of the solvent and catalyst, shown in the following Table, hereafter are cooled to -60°C and ,1.8 g hydrogen sulfide is added. Each of the mixtures is sealed in a pressure bottle and warmed to the indicated temperature. After the specified reaction time, the mixture is diluted with chloroform and analyzed by gas liquid chromatography against triphenylmethane internal standard I(OV 17; 90-280°C) to yield the indicated percent conversion for each of the respective loweralkyl 1-methylpyrrole-2-acetates obtained as corresponding products.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Priority Applications (3)

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Publications (2)

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Family Applications (1)

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Citations (6)

• 1978
  • 1978-10-27 DE DE7878101245T patent/DE2862262D1/de not_active Expired
  • 1978-10-27 EP EP19780101245 patent/EP0010553B1/de not_active Expired
• 1985
  • 1985-12-30 MY MY993/85A patent/MY8500993A/xx unknown

Patent Citations (6)

Non-Patent Citations (1)

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